The measurement of plasma steady-stage amitriptyline and nortriptyline levels is being made in carefully selected depressed outpatients during a six-week acute treatment period and five-month long-term follow-up. Severity of depression is being measured using the Hamilton depression rating scale and the Zung self-rating scale. Side effects are also monitored. An attempt will be made to define the plasma levels which produce maximum clinical response in a well described population. In addition, the design is such that the therapeutic effect of amitriptyline and nortriptyline can be compared whenever plasma levels of the two drugs are measured. The long-term follow-up portion of the study will provide information regarding the prophylactic value of tricyclic antidepressants in preventing depressive relapses, whenever plasma levels are maintained within the previously defined therapeutic range. Initial data indicate that there is a significiant negative correlation between Hamilton scores and the mean total tricyclic level in patients treated with amitriptyline. Tricyclic plasma levels are also being measured in patients ingesting primarily tricyclic antidepressant overdoses. The purpose of this project is to correlate medical symptoms with drug plasma levels. Overdose patients also provide a model for studying differences in the degree of toxicity among the various commonly used tricyclic antidepressants. Various medical treatments can be documened using plasma tricyclic levels to define the seriousness of the drug ingestion. BIBLIOGRAPHIC REFERENCES: Spiker DG, Weiss AN, Chang SS, Ruwitch JF, Biggs JT: Tricyclic antidepressant overdose: clinical presentation and plasma levels. Clin Pharmacol Ther 18: 539-546, 1975. Biggs JT, Chang SS, Sherman WR, Holland WH: Measurement of tricyclic antidepressant levels in an outpatient population. J Nerv Ment Dis 162: 46-51, 1976.